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BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro
BACKGROUND: Heart disease could result from a malfunction in the core clock gene BMAL1, according to studies conducted on animals and humans in vitro and in vivo. However, in pathological conditions, the role of BMAL1 was not clear. In the present study, we identified a potential link between BMAL1...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396899/ https://www.ncbi.nlm.nih.gov/pubmed/35996077 http://dx.doi.org/10.1186/s12872-022-02822-3 |
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author | Yu, Lei Ren, Lei Dong, Linchang |
author_facet | Yu, Lei Ren, Lei Dong, Linchang |
author_sort | Yu, Lei |
collection | PubMed |
description | BACKGROUND: Heart disease could result from a malfunction in the core clock gene BMAL1, according to studies conducted on animals and humans in vitro and in vivo. However, in pathological conditions, the role of BMAL1 was not clear. In the present study, we identified a potential link between BMAL1 and cardiac hypertrophy. METHODS: Primary cultured neonatal rat cardiomyocytes were stimulated by Ang II. Cardiomyocytes immunofluorescence analysis was performed to observe the cell size. RT-PCR and Western blot were used to find out the gene and protein expression. Cell apoptosis was measured by TUNEL staining. The Elisa assay was performed which determine the release of cytokines led to the activation of cardiac fibro-blasts in cell-free supernatants. Furthermore, gain- and loss-of-function studies revealed that BMAL1 has an effect on Ang II-induced cardiac hypertrophy. RESULTS: We found that Ang II-induced cardiac hypertrophy as a result BMAL1 expression was reduced. However, overexpression of BMAL1 could prevent Ang II-induced hypertrophy. Additionally, although BMAL1 overexpression in hypertrophic cardiomyocytes could not prevent hypertrophy, it did reduce the apoptosis of hypertrophic cardiomyocytes after Ang II had induced it. In addition, BMAL1 knockdown did not aggravate Ang II-induced hypertrophy but accelerated its development. Finally, BMAL1 overexpression significantly resisted the effects of Ang II on oxidative stress, autophagy and, cardiac fibrosis in cardiomyocytes. CONCLUSIONS: Our results showed that overexpression of BMAL1 effectively resisted cardiac hypertrophy induced by Ang II. Our findings provided a novel potential target for the treatment of cardiac hypertrophy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02822-3. |
format | Online Article Text |
id | pubmed-9396899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93968992022-08-24 BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro Yu, Lei Ren, Lei Dong, Linchang BMC Cardiovasc Disord Research BACKGROUND: Heart disease could result from a malfunction in the core clock gene BMAL1, according to studies conducted on animals and humans in vitro and in vivo. However, in pathological conditions, the role of BMAL1 was not clear. In the present study, we identified a potential link between BMAL1 and cardiac hypertrophy. METHODS: Primary cultured neonatal rat cardiomyocytes were stimulated by Ang II. Cardiomyocytes immunofluorescence analysis was performed to observe the cell size. RT-PCR and Western blot were used to find out the gene and protein expression. Cell apoptosis was measured by TUNEL staining. The Elisa assay was performed which determine the release of cytokines led to the activation of cardiac fibro-blasts in cell-free supernatants. Furthermore, gain- and loss-of-function studies revealed that BMAL1 has an effect on Ang II-induced cardiac hypertrophy. RESULTS: We found that Ang II-induced cardiac hypertrophy as a result BMAL1 expression was reduced. However, overexpression of BMAL1 could prevent Ang II-induced hypertrophy. Additionally, although BMAL1 overexpression in hypertrophic cardiomyocytes could not prevent hypertrophy, it did reduce the apoptosis of hypertrophic cardiomyocytes after Ang II had induced it. In addition, BMAL1 knockdown did not aggravate Ang II-induced hypertrophy but accelerated its development. Finally, BMAL1 overexpression significantly resisted the effects of Ang II on oxidative stress, autophagy and, cardiac fibrosis in cardiomyocytes. CONCLUSIONS: Our results showed that overexpression of BMAL1 effectively resisted cardiac hypertrophy induced by Ang II. Our findings provided a novel potential target for the treatment of cardiac hypertrophy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02822-3. BioMed Central 2022-08-22 /pmc/articles/PMC9396899/ /pubmed/35996077 http://dx.doi.org/10.1186/s12872-022-02822-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yu, Lei Ren, Lei Dong, Linchang BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title | BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title_full | BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title_fullStr | BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title_full_unstemmed | BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title_short | BMAL1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
title_sort | bmal1 plays a critical role in the protection against cardiac hypertrophy through autophagy in vitro |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396899/ https://www.ncbi.nlm.nih.gov/pubmed/35996077 http://dx.doi.org/10.1186/s12872-022-02822-3 |
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